Search Results (14,598)

Background: Postmenopausal osteoporosis is a common metabolic bone disorder characterized by decreased bone mass and microstructural deterioration, often accompanied by increased bone marrow adiposity and systemic fat accumulation. Kun-Ling Wan Formula (KLW) is a compound Chinese medicine clinically used for gynecological disorders, though its effects on postmenopausal osteoporosis and associated fat accumulation remain unclear. Distinct from previous herbal formulation studies that primarily focused on bone outcomes, our study uniquely integrates bone protection, marrow adiposity reduction, systemic metabolic improvement, and multi-omics mechanistic dissection in a high-fat diet-fed ovariectomized mouse model. Methods: KLW chemical composition was analyzed by UPLC-Q-TOF/MS. Ovariectomized (OVX) C57BL/6J mice fed high-fat or normal diet were treated with KLW at clinically equivalent or double doses, with estrogen and active compounds as controls. Bone microstructure was assessed by micro-CT, bone marrow fat by MRI-PDFF, and metabolism by OGTT, ITT, and metabolic cages. Network pharmacology, proteomics, molecular docking, and dynamics simulations identified core targets. C3H10T1/2 cells were used to assess osteogenic/adipogenic differentiation and mTOR pathway activation. Results: Twelve compounds were identified in KLW. In OVX mice, KLW significantly improved bone mineral density and trabecular microstructure, reduced adiposity and bone marrow fat, and enhanced glucose tolerance and insulin sensitivity. In vitro, KLW promoted osteogenesis and suppressed adipogenesis in C3H10T1/2 cells. Integrative analyses identified mTOR as a central target, with chrysophanol, pyrogallol, and apigenin showing high-affinity binding. KLW inhibited mTOR/S6K phosphorylation during differentiation, an effect reversible by leucine. Conclusions: KLW ameliorates osteoporosis and reduces fat accumulation in OVX mice by shifting mesenchymal stem cell differentiation toward osteogenesis via mTOR pathway modulation. Full article

Ponatinib, a third-generation BCR::ABL1 inhibitor, has antileukemic activity but is associated with cardiovascular toxicity, for which transcriptome-level responses remain incompletely characterized. Here, we defined a ponatinib-associated transcriptomic signature and examined its mechanistic implications using two public RNA sequencing (RNA-Seq) datasets: GSE186341 (11 cancer cell lines treated with kinase inhibitors) and GSE217421 (induced pluripotent stem cell (iPSC)-derived cardiomyocytes treated with approved drugs). Principal component analysis (PCA) and k-means clustering were used to define expression-based subgroups of vehicle-treated (DMSO) controls. DESeq2, followed by fixed-effect meta-analysis, estimated subgroup-specific treatment effects and pooled effect estimates across subgroups. In GSE186341, we identified 2,639 meta-analytic differentially expressed genes (meta-DEGs). Among these, 81 genes were also differentially expressed in GSE217421 after ponatinib treatment, identifying an overlapping gene set across datasets. In contrast, imatinib showed no overlap with these 81 genes under the same cross-dataset analysis framework. Cardiotoxicity-relevant functions were represented by directionally consistent genes linked to cardiac repolarization-associated ion handling (KCNN3), insulin-responsive metabolic regulation (FOXO1, HK2), cyclic adenosine monophosphate (cAMP)-responsive stress signaling (RAPGEF3), and mitochondrial homeostasis and redox regulation (MCL1, GCH1). Collectively, these results define a ponatinib-associated transcriptomic signature and nominate cross-dataset transcript-level candidates for subsequent mechanistic and experimental validation in ponatinib-associated cardiotoxicity. Full article

Purpose: Natural polysaccharides have shown considerable potential in the management of type 2 diabetes mellitus (T2DM) due to their multi-target metabolic regulatory effects. However, their clinical translation is limited by poor oral stability and low intestinal permeability. Snow lotus polysaccharide (SIP), a representative plant-derived polysaccharide, exhibits promising metabolic benefits but suffers from these delivery barriers. This study aimed to develop an oral nanodelivery system to enhance the gastrointestinal stability and intestinal transport of SIP, thereby improving its in vivo efficacy. Methods: SIP-loaded chitosan–tripolyphosphate nanoparticles (SIP@CS-TPP) were prepared via ionic crosslinking and characterized in terms of particle size, surface charge, morphology, and structural features. In vitro release behavior under simulated gastrointestinal conditions was evaluated. Ex vivo intestinal permeation was assessed using an isolated intestinal sac model. The metabolic regulatory effects were further investigated in a high-fat diet/streptozotocin-induced T2DM rat model. Results: SIP@CS-TPP nanoparticles exhibited a uniform particle size of 188.9 ± 12.8 nm, a surface charge of 28.3 ± 5.1 mV, and good stability after freeze-drying. A pH-responsive and diffusion-controlled release profile was observed. Ex vivo studies demonstrated significantly enhanced intestinal transport, with an approximately 3.7-fold increase in apparent permeability compared with free SIP. In vivo, SIP@CS-TPP improved glycemic control, glucose tolerance, insulin resistance, lipid metabolism, oxidative stress, and inflammatory responses more effectively than free SIP at the same dose. Conclusions: The CS-TPP nanodelivery system effectively enhances the oral delivery and metabolic regulatory effects of SIP. This study highlights the potential of a delivery-oriented strategy to improve the in vivo performance of natural polysaccharides and provides a promising approach for their application in metabolic disease management. Full article

Background/Objectives: Adolescence is a critical developmental period during which dietary quality and physical activity (PA) may influence insulin sensitivity and pancreatic β-cell function. This observational cohort study investigated how adherence to the Mediterranean diet (MedDiet) and participation in structured physical activity (PA) relate to metabolic changes over six months in Spanish male adolescents. Methods: A total of 78 participants (median age 11 years; IQR 10–12) were followed in a school-based study (2020–2021) and categorized by MedDiet adherence using the KIDMED index into medium (M) and high (H) groups. Metabolic health was assessed at baseline (T1) and after six months (T2) using lipid profiles, glucose, insulin, and several indirect indices of insulin resistance and β-cell function, including HOMA-IR, QUICKI, and SPINA indices. Statistical analyses included correlations and adjusted linear models, with false discovery rate correction applied. Results: At baseline, higher MedDiet adherence was associated with lower fasting insulin and improved insulin resistance markers (p ≤ 0.002). Over six months, adolescents with high adherence showed more favorable changes in insulin sensitivity (fasting insulin, HOMA-IR, QUICKI) and β-cell function (SPINA indices), with results remaining significant after correction (all pFDR < 0.05). LDL cholesterol levels also improved more markedly in participants combining high MedDiet adherence with structured PA (pFDR < 0.001). In contrast, triglycerides and TG-related indices increased across all groups, without differences between them (pFDR < 0.001). Conclusions: High MedDiet adherence combined with structured PA was associated with more favorable trajectories in insulin sensitivity, attenuated β-cell secretory demand, and a more favorable LDL-c profile. These findings support integrated lifestyle approaches for early cardiometabolic prevention in male adolescence. Full article

Background/Objectives: Type 2 diabetes mellitus (T2-DM) is a continuing national and global health challenge. Retinoic acid (RA), the major transcription-regulating ligand, plays a critical role in energy metabolism, and pancreatic β-cell homeostasis. However, human data linking circulating RA levels to T2-DM and its clinical outcomes are sparse and inconsistent. In this ethically approved cross-sectional study of consented hospital-diagnosed adult T2-DM patients (n = 292) and matched healthy controls (n = 64), variation in plasma RA levels and its relationship with disease and patient characteristics were investigated. Methods: RA concentrations assayed via specific ELISA were related to glycemic control indices [fasting blood glucose (FBG) and HbA1c], the triglyceride–glucose ratio for insulin resistance (TyG-IR), treatment modalities, and complications derived from patients’ medical records. Results: RA concentrations were substantially lower in patients with T2-DM (mean ± SD 2.63 ± 1.54 ng/mL) than in controls (5.21 ± 4.3 ng/mL; p < 0.001). Within the diabetic cohort, RA was inversely correlated with indices of glycemic dysregulation and insulin resistance. Plasma RA exhibited strong discriminatory performance for distinguishing diabetic patients from healthy adults. Its AUC is 0.870 (p < 0.0001 and 95% CI = 0.832–0.902) with a sensitivity of 79.7% and a specificity of 81.3%, at an optimal cutoff of ≤3.061 ng/mL. Conclusions: Circulating RA is associated with metabolic perturbations that define T2-DM, and therefore is promising as a clinically useful biomarker. It may reflect pathophysiological processes linking nutrient signaling, energy handling and β-cell function in T2-DM that merit further evaluation. Full article

Background/Objectives: It is estimated that one in three adults in the US has one or more risk factors for cardiovascular–kidney–metabolic (CKM) syndrome. The American Heart Association (AHA) has warned that the interaction between obesity, Type 2 diabetes (T2D), chronic kidney disease (CKD), and cardiovascular disease (CVD) leads to a multistage CKM syndrome with elevated mortality. This narrative review describes the newly coined terms CKM health and CKM syndrome, introduced by the AHA Presidential Advisory in 2023. Methods: In this narrative review, we will discuss the epidemiology and development of CKM syndrome, CKM stages, and the possible impact of precision nutrition on CKM and evaluate what is currently known about the role of nutrient metabolism in the physiological state and pathogenesis of CKM. Results: Since the AHA defined CKM syndrome in 2023, several studies have analyzed NHANES data to identify the correlations between CKM stages and adverse health outcomes. Studies also found that correlations between dietary intake and diet patterns may contribute to the protection against progression through various stages of CKM. However, experimental research and clinical studies are still lagging. Although the liver plays an integral role in nutrient metabolism, energy homeostasis, protein synthesis, nutrient storage, antibody production, and detoxifying compounds, it has not been included in the definition of CKM. Conclusions: Integrated body systems contribute to the development and progression of CKM. Precision nutrition and dietary patterns may play a role in the management of CKM and related comorbidities. Further research is warranted to address the role of precision nutrition in the prevention, early detection, and intervention in CKM syndrome as part of a comprehensive approach. It would be worth considering including metabolic dysfunction-associated liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) within the CKM framework. Full article

Prediabetes is increasingly recognized as a risk factor for sarcopenia, driven by chronic low-grade inflammation, insulin resistance, and impaired anabolic signaling. Nutritional interventions containing whey protein, hydroxymethylbutyrate (HMB), glucosamine, and micronutrients may offer a multi-target strategy to counteract muscle deterioration. This study aimed to evaluate the efficacy of HiLo Platinum™ supplementation in attenuating muscle strength decline in a prediabetic rat model, with integrated analysis of metabolic biomarkers and gut microbiome profiles. A randomized preclinical trial was conducted using male Sprague Dawley rats assigned to four groups: normal diet (ND), prediabetic control induced by cholesterol- and fat-enriched diet with fructose (CFEDF), and two treatment groups receiving low-dose (0.63 g/kg BW) or high-dose (1.26 g/kg BW) HiLo Platinum™. The intervention lasted six weeks. Muscle strength was assessed via a four-limb grip strength test (reverse hang time and holding impulse). Biomarkers related to inflammation, mitochondrial function, and anabolic signaling (TNF-α, IL-10, PGC-1α, IGF-1, SIRT-1, AMPK, mTOR, and myostatin), lipid profile, and blood glucose were analyzed. Gut microbiome composition and diversity were evaluated using taxonomic profiling and multivariate analyses. HiLo Platinum™ supplementation significantly improved muscle strength, evidenced by increased reverse hang time and holding impulse (p < 0.001). Both doses reduced blood glucose and improved lipid profiles, including increased HDL and decreased LDL, triglycerides, and total cholesterol. Anti-inflammatory effects were observed with reduced TNF-α and elevated IL-10 levels. Mitochondrial and metabolic regulators (PGC-1α, SIRT-1, AMPK) and anabolic mediators (IGF-1) were significantly upregulated, while mTOR levels decreased. Gut microbiome analysis revealed increased genus richness (Chao1 index) and distinct microbial shifts associated with improved metabolic and inflammatory markers. HiLo Platinum™ effectively mitigates prediabetes-induced muscle strength decline through integrated modulation of inflammatory pathways, mitochondrial function, metabolic homeostasis, and gut microbiome composition. These findings support its potential as a nutritional therapeutic strategy for preventing sarcopenia in prediabetic conditions, although further studies are needed to evaluate long-term effects and implications on muscle hypertrophy. Full article

This study evaluated the protective effects of green coffee (Coffea arabica L.) extract (GCE) against metabolic and endocrine disturbances induced by fipronil (FIP) in male rats. Animals were randomly allocated into four groups (n = 6): control, GCE (100 mg/kg), FIP (4.85 mg/kg), and combined FIP + GCE, and treated orally for 90 days. FIP exposure significantly impaired glucose homeostasis, as indicated by a 14.8% increase in the oral glucose tolerance test (OGTT) response and a 2.4-fold increase in the homeostatic model assessment of insulin resistance (HOMA-IR). It also disrupted lipid metabolism, with marked elevations in triglycerides (74.10%) and total cholesterol (57.55%). Endocrine imbalance was evident, including increased resistin levels (113.86%) and reduced triiodothyronine (T3; −37.5%), adiponectin (−42.73%), and high-density lipoprotein (HDL; −9.31%). Oxidative stress and inflammation were significantly enhanced, as demonstrated by elevated malondialdehyde (MDA; +93.56%) and pro-inflammatory cytokines (IL-1β: +246.56%; IL-6: +275%), alongside a reduction in total antioxidant capacity (TAC; −45.24%). Additionally, serum albumin levels decreased markedly (−54%). Co-administration of GCE significantly improved metabolic, hormonal, and inflammatory parameters, including insulin resistance (HOMA-IR). Histopathological analysis further confirmed its protective effects on hepatic and renal tissues. Overall, GCE mitigates FIP-induced metabolic and endocrine dysfunction, likely through its antioxidant and anti-inflammatory properties. Full article

Background: Effective glycemic control in diabetes management relies heavily on dietary carbohydrate knowledge. This study aimed to assess carbohydrate knowledge in individuals with type 1 diabetes (T1D) and insulin-treated type 2 diabetes (itT2D) using the GluciQuizz tool. Methods: A total of 465 persons (96 with T1D, 153 with itT2D; 89 and 127 matched controls without diabetes, respectively) from the French NutriNet-Santé prospective cohort were included. Participants completed the GluciQuizz questionnaire, which evaluates carbohydrate knowledge across five domains: carbohydrate food recognition; carbohydrate food content; nutrition label reading; glycemic targets and hypoglycemia prevention and treatment; and carbohydrate content of meals. Results: The mean age ± standard deviation of participants with diabetes was 65.8 ± 11.2 years, 44.2% male, with a diabetes duration of 23.3 ± 12.9 years. T1D participants scored significantly higher on the GluciQuizz compared to those with itT2D (23.9 ± 5.0 vs. 17.5 ± 5.6, p < 0.001). In secondary analysis, T1D participants showed superior knowledge to their matched controls without diabetes, whereas itT2D participants showed similar knowledge to their matched controls without diabetes. Conclusions: T1D participants demonstrated the best carbohydrate knowledge compared to those with itT2D. Targeted educational interventions in itT2D populations may improve dietary management and clinical outcomes. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, with advanced stages potentially progressing to hepatocellular carcinoma. It is a multifactorial condition associated with metabolic syndrome, diabetes, and hormonal imbalance, leading to metabolic alterations that are intensified by inflammation. An important additional factor that amplifies these effects is oxidative stress, which interacts with inflammatory pathways and contributes to disease progression. This review evaluates evidence from in vitro, in vivo, and clinical studies on widely investigated natural compounds, including cinnamic acid, stilbene and quinone derivatives, coumarinoids, tannins, and miscellaneous phenol-containing compounds and alkaloids, focusing on their antioxidant, anti-inflammatory and multi-functional properties. These compounds have demonstrated beneficial effects such as reduction of lipid accumulation, improvement of insulin resistance, modulation of inflammatory cytokines (e.g., TNF-α, IL-6), and attenuation of oxidative stress markers, with several studies reporting improvements in liver enzymes and histological features of steatosis. The aim is to assess their potential to improve NAFLD beyond their established biological activities and to explore their repositioning potential as multi-targeted agents for complementary or second-line therapeutic strategies. Their plant-derived origin and broad therapeutic profiles suggest a favorable safety margin. However, further well-designed clinical studies are required to better define their efficacy, optimal dosing, pharmacokinetics and safety, as well as to clarify their mechanisms of action and their potential role in NAFLD management. Full article

Potassium homeostasis is essential for maintaining membrane potential and normal neuromuscular function. Although potassium disturbances are clinically relevant in several species, their prevalence and prognostic significance in pet rabbits remain poorly characterized. This retrospective study evaluated plasma potassium concentrations at admission in 1773 venous samples from 1312 pet rabbits and assessed associations with mortality, glycemia, and renal markers (BUN and creatinine) using an i-Stat portable analyzer. Normokalemia (3.4–5.7 mmol/L) was observed in 78.1% of samples, while hypokalemia and hyperkalemia occurred in 13.9% and 8.0%, respectively. Overall, 7-day mortality was 21.3%, with most deaths (68.7%) occurring within 48 h. Both hypo- and hyperkalemia were associated with increased mortality, with hyperkalemia conferring the greatest risk (relative risk of up to 5.4 at 24 h; p < 0.0001). Potassium concentrations were higher in non-survivors at all time points. Hyperkalemia was also associated with hypoglycemia and azotemia (p < 0.0001), suggesting impaired renal potassium excretion and possible alterations in insulin-mediated cellular potassium uptake. No consistent association was observed between hyperglycemia and hyperkalemia. These findings indicate that plasma potassium disturbances are common in pet rabbits and are associated with short-term mortality and metabolic derangements. Early identification and correction of potassium imbalances and their causes may improve outcomes in critically ill rabbits. Full article

Background/Objectives: Fingered citron (Citrus medica L. var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle) is rich in phenolic constituents, yet systematic comparisons of free and bound phenolics across tissues and origins remain limited. This study compared the peel, pulp, and blend (whole fruit) of fingered citron from five Chinese regions: Zhejiang (ZJ), Yunnan (YN), Sichuan (SC), Guangdong (GD), and Guangxi (GX). Methods: Phenolic compositions were determined by colorimetric assays and HPLC. Antioxidant activity was assessed by ORAC and PSC, and hypoglycemic-related activity by α-glucosidase and α-amylase inhibition and glucose consumption in an insulin-resistant HepG2 (IR-HepG2) cell model. Results: Phenolic distribution followed the order peel > blend > pulp, and free > bound. HPLC identified 11 free and 5 bound phenolics, predominantly hesperidin, quercetin, and 5,7-dimethoxycoumarin. GX peel exhibited the highest free phenolic content (106.34 ± 0.23 mg GAE/100 g FW) and superior ORAC (30.56 ± 0.50 μmol TE/g FW), strongly correlating with total phenolics (r = 0.98, p < 0.01). Free phenolics showed stronger α-glucosidase and α-amylase inhibition, whereas bound phenolics produced higher glucose consumption in the IR-HepG2 cell model. The GX blend bound fraction showed the highest glucose consumption (5.48 ± 0.98 mmol/L). Conclusions: Under fresh-weight-based conditions, phenolic composition and in vitro bioactivities differed by fruit part, region, and phenolic fraction. Peel, especially GX peel, tended to show higher phenolic levels and stronger antioxidant-related performance, whereas the GX blend bound fraction showed the highest glucose-consumption-promoting activity. Full article

Cardiometabolic diseases, encompassing obesity, insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), hypertension, and atherosclerotic cardiovascular disease (ASCVD), represent a vast continuum driven by multi-organ network dysregulation. Clinical risk assessment remains dominated by late-stage measures (e.g., fasting glucose, HbA1c, standard lipids). While these assessments predominate the literature and clinical trial endpoints, each incompletely capture early mechanistic risk, inter-individual heterogeneity, and differential response to interventions. Multiomics (genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, microbiomics, and extracellular vesicle/exosome cargo profiling) expands the biomarker landscape but introduces translational barriers: high dimensionality, cohort heterogeneity, limited causal inference, and insufficient validation pipelines. AI-driven systems biology platforms can support cardiometabolic biomarker discovery and therapeutic translation by enabling systems-level biological inference across heterogeneous datasets, prioritizing mechanism and traceability over purely correlation-based models. GATC Health’s Operon™ platform is described as a proprietary, AI-driven internal scientific computing platform designed to support therapeutic discovery and development decision-making across the pharmaceutical lifecycle, including evaluation of drug efficacy, safety, off-target effects, pharmacokinetics (PK), pharmacodynamics (PD), and overall development risk. Operon evolved from earlier generations of GATC Health’s internal multiomic modeling systems (formerly referred to as the Multiomics Advanced Technology, MAT) and incorporates expanded data types, orchestration layers, validation workflows, and productization frameworks. Operon is operated by GATC scientists and generates structured, productized outputs (e.g., formal assessments, analyses, and decision frameworks) that are reviewed by experts. Operon methodologies have undergone internal validation and independent academic evaluation under blinded conditions, with reported classification performance (true positive rate 86% and true negative rate 91%) in controlled evaluation settings; these performance metrics should not be interpreted as guarantees of clinical success. This review provides a T2D-centered cardiometabolic biomarker landscape with cardiovascular extension and outlines how Operon-enabled multiomic integration and scenario-based simulation can support early screening, endotype stratification, mechanistic interpretation, and precision intervention design, including AI-guided polypharmacology strategies. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Background: The triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, has been increasingly associated with adverse cardiometabolic outcomes. However, its relationship with acute kidney injury (AKI) across clinical settings has not been comprehensively synthesized. We performed a systematic review and meta-analysis to evaluate the association between the TyG index and AKI risk. Methods: PubMed, Embase, and Web of Science were searched through February 2026 for observational studies reporting adjusted associations between TyG and AKI. Random-effects models were used to pool categorical and continuous effect estimates. Dose–response analyses and subgroup assessments were conducted to explore consistency. Diagnostic performance was summarized when available. Results: Thirty studies involving 518,677 participants were included. Compared with the lowest-TyG category, the highest-TyG category was associated with significantly increased AKI risk (pooled OR = 1.95, 95% CI 1.66–2.28; I² = 72.7%). Associations were most consistently observed in cardiovascular disease cohorts (pooled OR = 1.86, 95% CI 1.44–2.40) and remained directionally similar across other clinical settings without significant subgroup interactions. Each 1-unit increment in TyG index was associated with higher AKI risk (OR = 1.48, 95% CI 1.30–1.69), and time-to-event analyses yielded concordant results (HR = 1.38, 95% CI 1.14–1.65). A significant non-linear dose–response association was observed (p < 0.001). The TyG index showed moderate discrimination (AUC = 0.74), with findings remaining robust in sensitivity analyses. Conclusions: Current evidence supports TyG primarily as a complementary metabolic risk marker rather than a substitute for established AKI diagnostic or prediction tools. TyG may serve as a practical marker for metabolic risk stratification in patients at risk of AKI. Full article